Runx-2 gene deletion leads to the complete loss of osteoblasts in mice [93, 94], and the mutation of Runx-2 in humans causes cleidocranial dysplasia (CCD), which is an autosomal dominant disease that causes significant abnormalities in bones due to intramembranous ossification [95]; these findings suggest that Runx-2 is the master gene for osteoblast differentiation [96, 97]. This evidence concerns the gene RUNX2 and cleidocranial dysplasia 1.